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Semaglutide targets muscle mitochondria to regulate osteoarthritis

ABSTRACT:

Metabolic and inflammatory diseases often coexist, and become important challenges facing global health, and obesity has shown to be a susceptibility factor for osteoarthritis (OA). As a metabolic regulatory drug for lowering blood sugar and body weight, semaglutide has shown additional therapeutic effects in OA, but the underlying mechanism requires further investigation. Here we employed cross-tissue single-cell RNA sequencing (scRNA-seq) analysis, and found that semaglutide significantly improved metabolic disorders in muscle tissue under high-fat diet (HFD) and OA conditions in mice. The results of scRNA-seq and mitochondrial proteomics indicated that semaglutide targeted muscle mitochondria to regulate glutamate metabolism during OA. Intriguingly, intramuscular injection of semaglutide pre-stimulated mitochondria from muscle stem cell could significantly alleviate OA inflammation and pain symptoms. These findings reveal the mitochondrial regulatory mechanism in the muscle-OA axis, and provide a new perspective for the application of semaglutide in OA treatment.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS14059 | MetaboLights | 2026-05-06

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS14059_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS14059_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS14059_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS14059_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Semaglutide targets muscle mitochondria to regulate glutamine metabolism and treat osteoarthritis

Project description:<p>Metabolic and inflammatory diseases often coexist, and become important challenges facing global health, and obesity has shown to be a susceptibility factor for osteoarthritis (OA). As a metabolic regulatory drug for lowering blood sugar and body weight, semaglutide has shown additional therapeutic effects in OA, but the underlying mechanism requires further investigation. Here we employed cross-tissue single-cell RNA sequencing (scRNA-seq) analysis, and found that semaglutide significantly improved mitochondrial metabolic disorders in muscle tissue under high-fat diet (HFD) and OA conditions in mice. The results of metabolome and mitochondrial proteomics indicated that semaglutide targeted muscle mitochondria to regulate glutamine metabolism during OA. Intramuscular injection of semaglutide pre-stimulated mitochondria from myoblasts could significantly alleviate OA inflammation and pain symptoms, which was achieved by inhibiting muscle glutaminase activity, upregulating circulating glutamine concentration, and thereby alleviating cartilage inflammation. In vitro experiments further confirmed the alleviating effect of glutamine produced by myoblasts stimulated by semaglutide on chondrocyte inflammation. These findings reveal the mitochondrial regulatory mechanism in the muscle-OA axis, and provide a new perspective for the application of semaglutide in OA treatment.</p>

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